Could a Blood Test Help Detect Anxiety Disorders?

A test that detects signs of anxiety in the blood could be a game-changer for mental health care, a new study shows.¹

Nearly one-third of adults in the United States experience an anxiety disorder at some point in their lives, but finding the proper treatment for each unique situation can be a long process.² A novel blood test, developed by researchers at the University of Indiana, could help doctors diagnose, treat and monitor anxiety in patients.

“Most patients are complex, with some cognitive abnormalities, mood abnormalities, and anxiety. This is a better assessment of all of those areas so you can have a comprehensive view,” the study’s lead author, Alexander B. Niculescu, MD, PhD, a professor of psychiatry at Indiana University School of Medicine, told Health. “It’s not just the traditional approach that we use, putting a single label on a patient.”

Designing a Blood Test to Detect Anxiety

The new test—currently available through the start-up MindX Sciences—is the product of two decades of tedious work.¹

Biomarkers are commonly used to diagnose, monitor and treat cancer with precision by detecting circulating pieces of RNA and DNA in a liquid biopsy, or blood sample.³ The presence of certain genes that are either turned on or off can tell doctors how well a person is responding to treatment. But using the same biopsy approach for mental health conditions has proven to be difficult. 

“In psychiatry, everything is more difficult than other areas of medicine because we don’t have tissue,” explained Edwin van den Oord, PhD, director of the Center for Biomarker Research and a professor of precision medicine at Virginia Commonwealth University in Richmond, Virginia, who was not involved in the new research.

For this reason, Dr. Niculescu had to first run a series of studies to tease out which gene and specific gene expressions—whether or not the gene is “on” or “off”—are associated with anxiety disorder. 

“What really mattered was to be accurate,” Dr. Niculescu stated, noting that the team also wanted to understand how to detect a genetic signature that correlates to something that is happening in the brain, rather than in the tissues of the body, as is the case in cancer. 

It was plausible, since the brain and the immune are closely linked.⁴ 

“There is a two-way communication between them, the brain affects the immune system and the immune system affects the brain,” Dr. Niculescu explained. “That’s how we can pick some peripheral signal that is picking up what is happening in the brain.”

The research team had to carry out whole genome sequencing on RNA in blood samples to identify which genes and expressions appeared to be more prevalent in people with anxiety, and what genes tended to look like in people who were not anxious.¹ That information was then compared to genetic information taken from a larger cohort of patients. A third study evaluated the data further, comparing it to even more patients.

Dr. Niculescu compared the process to a search engine. The more relevant a gene expression appeared to be, the higher on the list it would bump up. The irrelevant ones would drop to the bottom and his team would rule those ones out as potential indicators of anxiety.

The biomarkers that rose to the top in those first three studies were tested in a clinical setting to see whether or not they could predict who had anxiety, would develop anxiety, and whose anxiety was most likely to become severe in the future.¹

Using that information, Dr. Niculescu and his team were able to develop an approach that uses liquid biopsies, like those used in cancer care, to identify gene expression signatures that can track the severity of peoples’ anxiety and determine which treatments they will likely respond to best.

“Having the ability to improve prescribing existing drugs to patients could be a major leap forward,” noted Dr. van den Oord.

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Precise Tests Boost Mental Health Treatment

There’s rarely a smooth, fool-proof method for prescribing treatments, including medication, for anxiety disorders. That reality can lead to months, or even years, of trying treatments that don’t work for a patient. 

“It is not always possible for people to self-report on the root cause of their experiences simply through reflecting on these experiences,” explained Leanne Williams, PhD, founding director of the Stanford Center for Precision Mental Health and Wellness and the Stanford PanLab for Precision Psychiatry and Translational Neuroscience at Stanford University.

Dr. Williams compares the recent progress in using objective testing, which provides test results rather than relies on a patient’s reported symptoms, in mental health to changes in heart disease treatment seen over the past 75 years.

“We have moved from a reliance on self-report for heart disease to the routine use of advanced imaging and other biomarkers to make an accurate diagnosis and to select the right treatment accordingly,” she told Health.

Dr. Williams continued, “the brain is orders of magnitude more complex. We need similarly advanced imaging and biomarker tests to more precisely understand the root cause of each person’s disorder and what treatment will be most beneficial for them.”

Dr. Niculescu’s past research has helped develop similar blood tests for pain, depression, and bipolar disorder, and post-traumatic stress disorder (PTSD).⁵ He stressed that the new blood test for anxiety, and any that may follow, should be used in conjunction with the evaluations doctors already use to diagnose mental health conditions. He sees the tool being most useful for primary care providers—they see a large number of patients and can easily add an additional blood test to a visit.

Once a person starts treatment, biomarkers can help manage the entire lifecycle of an anxiety disorder. The test also helps recognize anxiety as a condition that is not benign, or “all in someone’s head.”

“People suffer in silence,” Dr. Niculescu concluded. “But anxiety is another biological abnormality that can be identified, monitored, and treated.”